Therapy for Advanced NSCLC With EGFR 19delins Mutation

March 4, 2026 updated by: Fuzhou General Hospital

A Comparative Study on the Efficacy of First-generation Versus Third-generation EGFR TKIs as First-line Therapy for Advanced NSCLC With EGFR Exon 19 Deletion-insertion (19delins) Mutation

In a retrospective analysis of 3,054 advanced NSCLC patients, 41 with EGFR exon 19 deletion-insertions (19delins) received first-generation EGFR TKIs, achieving median PFS of 10.4 months; those with L747_T751delinsP had notably longer PFS of 18.7 months. Another study of 2,467 treatment-naïve patients found 93 with 19delins treated with first-generation TKIs had median PFS of 19 months, exceeding the 13 months for common 19del mutations. For third-generation TKIs, a study of 215 19delins patients (57 first-line) showed median PFS of 12.9 months, inferior to 23.2 months for common 19del. Our center's retrospective study of 4,666 NSCLC patients in Fujian (2017-2020) included 69 with 19delins: median PFS was 16.7 months with first-generation TKIs versus 7.2 months with third-generation. Evidence suggests specific EGFR deletion locations may affect TKI efficacy; first-generation TKIs may be superior in some 19delins subtypes, while third-generation appear limited. Large prospective data are lacking. This project aims to compare first- versus third-generation EGFR TKIs in 19delins patients via a randomized controlled trial, stratify sensitivity by subtype, and improve survival.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

In a retrospective analysis of 3,054 patients with advanced non-small cell lung cancer (NSCLC), a total of 41 patients with EGFR exon 19 deletion-insertion mutations (19delins) were enrolled, all of whom received first-generation EGFR TKIs. The results showed a median progression-free survival (PFS) of 10.4 months, among which patients with L747_T751delinsP had a median PFS of 18.7 months, which appeared superior to that of patients with other 19delins mutations.

Another retrospective study analyzed 2,467 treatment-naïve patients with locally advanced NSCLC, among whom 93 patients with EGFR exon 19delins mutations were treated with first-generation EGFR TKIs (gefitinib, erlotinib). The median PFS was 19 months in patients with EGFR 19delins mutations, which was longer than that (13 months) in patients with common EGFR 19del mutations treated with first-generation EGFR TKIs during the same period.

However, regarding third-generation EGFR TKIs, a retrospective study enrolled 215 patients with EGFR 19delins mutations, including 57 patients treated with third-generation EGFR TKIs (osimertinib, furmonertinib, aumolertinib) as first-line therapy. The median PFS reached 12.9 months, which was lower than that (23.2 months) in patients with common EGFR 19del mutations.

This result is consistent with our center's previously published findings. A retrospective study of 4,666 NSCLC patients with EGFR mutations in Fujian Province from January 2017 to December 2020 included 69 patients with the EGFR exon 19delins subtype. The median PFS was 16.653 months in patients receiving first-generation EGFR TKIs and 7.179 months in those receiving third-generation EGFR TKIs.

Collectively, available evidence suggests that the specific location and structural variation type of EGFR deletions may affect the efficacy of different generations of TKIs. Especially for rare mutations such as 19delins, first-generation TKIs may show better efficacy in certain subtypes, while the efficacy of third-generation TKIs is relatively limited.

At present, large-scale prospective clinical data are still lacking for this type of mutation, and the optimal targeted therapeutic strategy remains to be further explored.

This project aims to clarify the efficacy and safety of first-generation versus third-generation EGFR TKIs in patients with EGFR exon 19delins mutations through a prospective, randomized controlled trial, further stratify the sensitivity of EGFR TKIs in patients with different EGFR mutation subtypes, and achieve longer survival benefits.

Study Type

Interventional

Enrollment (Estimated)

94

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥ 18 years;
  • Histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) (AJCC Cancer Staging Manual, 9th edition, Stage IIIB, IIIC or IV) that is not amenable or suitable for surgical resection or other radical therapies, as assessed by the investigator;
  • Epidermal growth factor receptor (EGFR) exon 19 deletion-insertion mutation (19delins) documented by testing of tumor tissue or plasma samples using methods including IHC, NGS, ARMS, etc.;
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1;
  • No prior systemic anti-tumor therapy for locally advanced or metastatic NSCLC;
  • Life expectancy ≥ 12 months;
  • At least one measurable lesion by imaging in the screening period according to RECIST v1.1;
  • Ability to swallow and retain oral medication;
  • Adequate organ system function;
  • Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days prior to initiation of study treatment, and agree to use a medically accepted highly effective method of contraception during the study and for 3 months after the last dose of study drug;
  • Voluntary and able to comply with study and follow-up procedures; Ability to understand the nature of the trial and provide written informed consent.

Exclusion Criteria:

  • Advanced and/or symptomatic brain metastases (measurable or non-measurable) and/or leptomeningeal metastases;
  • Active hepatitis B, positive for hepatitis C virus antibody, positive for human immunodeficiency virus (HIV) antibody, or positive for Treponema pallidum antibody;
  • Women of childbearing potential with a positive serum pregnancy test within 7 days prior to initiation of treatment, pregnant or lactating women, or male and female subjects who are not using effective contraception or plan to conceive during the entire treatment period and for 3 months after the end of treatment;
  • Patients who have used any of the following medications within 14 days prior to the first dose or require concomitant use of such medications during treatment: drugs with a risk of causing QTc prolongation and/or torsade de pointes; strong inhibitors or strong inducers of CYP3A;
  • Underwent major surgery or immunotherapy within 4 weeks prior to the first dose; received radiation therapy within 2 weeks prior to the first dose;
  • Patients with imaging evidence of tumor invasion of major blood vessels, or those judged to have a very high likelihood of tumor invasion of critical blood vessels leading to fatal massive hemorrhage during the subsequent study period;
  • History of interstitial lung disease, drug-induced interstitial disease, or any clinically evident active interstitial lung disease; presence of idiopathic pulmonary fibrosis on baseline CT scan;
  • Other severe, acute, or chronic medical conditions that, in the investigator's opinion, may increase the risk associated with study participation or may interfere with the interpretation of study results, including uncontrolled diabetes mellitus, medical or psychiatric illnesses, or laboratory abnormalities;
  • Any other conditions deemed by the investigator to make the subject unsuitable for participation in this trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental group

First-generation EGFR TKIs, including but not limited to:

Icotinib: 125 mg per dose, three times daily Gefitinib: 250 mg per dose, once daily Administration shall be discontinued in case of tumor recurrence or intolerable toxicities during the treatment period.
Drug: Icotinib/Gefitinib
To explore the efficacy of first-generation EGFR TKIs versus third-generation EGFR TKIs in the first-line treatment of advanced NSCLC with EGFR 19delins mutation.
Other Names:
  • Befotertinib/Osimertinib/Furmonertinib
Other: Control group

Third-generation EGFR TKIs, including but not limited to:

Befotertinib: Oral administration, taken on an empty stomach or with food. 75 mg once daily (QD), 21 days per cycle. After one cycle of treatment, the dose shall be escalated to 100 mg QD if no CTCAE 5.0 grade ≥2 thrombocytopenia or headache occurs; otherwise, 75 mg QD shall be maintained.

Osimertinib: 80 mg per dose, once daily Furmonertinib: 80 mg per dose, once daily Administration shall be discontinued in case of tumor recurrence or intolerable toxicities during the treatment period.
Drug: Icotinib/Gefitinib
To explore the efficacy of first-generation EGFR TKIs versus third-generation EGFR TKIs in the first-line treatment of advanced NSCLC with EGFR 19delins mutation.
Other Names:
  • Befotertinib/Osimertinib/Furmonertinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PFS
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.
Progression Free Survival
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
OS
Time Frame: From date of randomization until the date of death from any cause, assessed up to 60 months.
Overall Survival
From date of randomization until the date of death from any cause, assessed up to 60 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fuzhou General Hospital

Investigators

  • Study Director: Yu Zongyang, PhD, The 900th Hospital of Joint Logistic Support Force PLA

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

March 30, 2026

Primary Completion (Estimated)

October 30, 2030

Study Completion (Estimated)

October 30, 2030

Study Registration Dates

First Submitted

March 1, 2026

First Submitted That Met QC Criteria

March 4, 2026

First Posted (Actual)

March 9, 2026

Study Record Updates

Last Update Posted (Actual)

March 9, 2026

Last Update Submitted That Met QC Criteria

March 4, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025-209

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Lung Cancer

Clinical Trials on Icotinib/Gefitinib

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Latvia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe